ANANDAMIDE REGULATES THE EXPRESION OF HETERODIMERIC CYTOKINES OF THE NEW FAMILY OF IL-12 IN MICROGLIA/MACROPHAGE CELLS.

CORREA FG., DOCAGNE F., MESTRE-NIETO L., CLEMENTE D. AND GUAZA C.

Amsterdam - Países Bajos

Conferencia; VII. European Meeting on Glial Cell Functions in Health and Disease; 2005

Cytokines are mediators of the immune response which are synthesized mainly by accessory cells of the immune system, namely microglia/macrophages, monocytes, dendritic cells, etc. These molecules play an important role in the activation of T cells in the development of human inflammatory diseases, such as multiple sclerosis, viral encephalitis, and possibly post-traumatic processes. IL-12 (formed by subunits p35 and p40) and the recently described IL-23 (formed p19 and p40) and IL-27 (formed by p28 and EBI3) are a new family of heterodimeric cytokines with critical functions in the activation of the immune system in several models of CNS inflammation. These cytokines act in a secuential fashion: IL-27 primes naïve T cells, IL-12 fully activates primed T cells making them proliferate and differentiate to a Th1 respones, and IL-23 activates mainly memory T cells. Since IL-12 and IL-23 share the subunit p40, synthesis of this protein is tightly regulated, and is absent in unstimulated conditions. Dysregulated IL-12 or IL-23 gene expression may contribute to the initiation and perpetuation of various autoimmune and inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, Crohn’s disease, etc. Anandamide is an endogenous cannabinoid whose production is enhanced during infammatory conditions and it has anti-inflammatory properties. Since both anandamide and IL-12, and their related cytokines, are produced in situations of infammatory stimuli, and given the anti-inflammatory properties of anandamide; our aim was to study the possible effects of this endogenous compound in the synthesis of the differents subunits composing the IL-12-related cytokines family, focusing on the regulation of p40 production. We performed both studies in vitro and in vivo, and from our preliminar data we conlude that anandamide is able to regulate the expression of the distincts subunits of these cytokines by a receptor independent mechanism.